| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg | |||
| Other Sizes |
| Targets |
GR[1]
Dazucorilant is a non-steroidal small molecule that selectively binds to the Glucocorticoid Receptor (GR) with high affinity (Ki < 1 nM). It functions as a complete antagonist in certain cell types, blocking the effects of endogenous glucocorticoids, which makes it a valuable tool for studying the role of the GR in neuroinflammation and neurodegeneration. |
|---|---|
| ln Vitro |
Dazucorilant functions as a complete antagonist in human hepatocytes or HepG2 human cells since it can both provide non-measurable agonist activity in the absence of dexamethasone and stop the rise in TAT activity brought on by dexamethasone[3].
In cell-free assays, Dazucorilant binds to the GR with a Ki of <1 nM.In vitro, it functions as a complete antagonist in human hepatocytes or HepG2 cells, showing no measurable agonist activity in the absence of dexamethasone and fully blocking the rise in TAT (tyrosine aminotransferase) activity induced by the GR agonist dexamethasone. |
| ln Vivo |
Dazucorilant (30 mg/kg/day; SC) causes mice to exhibit glial reactivity, down-regulated proinflammatory mediators, and motoneurons with abnormalities reversed[1]. At a dose of 10 mg/kg, dazucorilant (5, 10 or 20 mg/kg; ip) improves cognitive function by reversing the production of amyloid-β peptides in the hippocampus, as well as neuroinflammation and apoptotic processes. It also restores the levels of synaptic markers in the hippocampus and baseline plasma levels of glucocorticoids.
In vivo, Dazucorilant (30 mg/kg/day, subcutaneous) reverses motoneuron abnormalities and down-regulates proinflammatory mediators and glial reactivity in a Wobbler mouse model of neurodegeneration.At doses of 10 mg/kg (intraperitoneal), it reverses neuroinflammation and apoptotic processes in the hippocampus, restores synaptic marker levels, and improves cognitive function. |
| Enzyme Assay |
Cell-free binding assays are performed using a radioligand competition binding format. The glucocorticoid receptor is incubated with a radiolabeled high-affinity ligand (e.g., 3H-dexamethasone) and varying concentrations of the test compound. After incubation at 4degC for 12 hours, the bound and free radioligands are separated, and the Ki value is calculated.
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| Cell Assay |
Cellular assays are conducted in HepG2 human hepatoma cells to assess its antagonist activity. Cells are treated with Dazucorilant in the presence or absence of a fixed concentration of dexamethasone (a potent GR agonist). Transcriptional activity is measured by quantifying TAT (tyrosine aminotransferase) activity, a GR-responsive gene, or by using a GR-luciferase reporter system.
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| Animal Protocol |
Animal/Disease Models: Wobbler mice (five-month-old)[1]
Doses: 30 mg/kg/day Route of Administration: Sc Experimental Results: Wobbler mice demonstrated reversed abnormalities of motoneurons and down-regulated proinflammatory mediators and glial reactivity. Animal/Disease Models: Adult SD male rats[2] Doses: 5, 10 or 20 mg /kg Route of Administration: Ip Experimental Results: Reversed hippocampal amyloid-β peptide generation, neuroinflammation and apoptotic processes, restored the hippocampal levels of synaptic markers, reestablished basal plasma levels of glucocorticoids and improved cognitive function at a dose of 10 mg/kg. In vivo studies are conducted in Wobbler mice, an animal model of motoneuron degeneration. Dazucorilant is administered subcutaneously at a daily dose of 30 mg/kg. Functional endpoints include assessment of motor function, histological analysis of spinal cord motoneurons, and immunochemical analysis of glial reactivity and proinflammatory mediators in neural tissues. |
| ADME/Pharmacokinetics |
The pharmacokinetic (PK) profile of Dazucorilant is currently being characterized. Studies indicate it is orally bioavailable and can be effectively delivered via intraperitoneal (ip) and subcutaneous (sc) routes, achieving effective concentrations in the central nervous system (CNS) to exert its neurological effects.
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| Toxicity/Toxicokinetics |
Dazucorilant has been evaluated in preclinical toxicity studies, which show it is generally well-tolerated at therapeutically relevant doses. The observed effects are primarily related to its pharmacological activity as a GR antagonist, with no significant off-target organ toxicities reported in initial studies.
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| References |
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| Additional Infomation |
Glucocorticoid receptor modulators; structure can be found in the first article.
Dazucorilant is a promising, non-steroidal GR modulator for neurological disorder research. As it can cross the blood-brain barrier and act as a complete antagonist, it represents a significant advancement over older GR modulators, potentially offering a safer profile for treating conditions like depression, cognitive impairment, and neurodegenerative diseases where GR dysregulation is implicated. |
| Molecular Formula |
C29H22F4N4O3S
|
|---|---|
| Molecular Weight |
582.5686
|
| Exact Mass |
582.134
|
| CAS # |
1496508-34-9
|
| PubChem CID |
72192163
|
| Appearance |
Off-white to light yellow solid powder
|
| LogP |
4.6
|
| Hydrogen Bond Donor Count |
0
|
| Hydrogen Bond Acceptor Count |
10
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
41
|
| Complexity |
1110
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
S(C1C([H])=C([H])C(C(F)(F)F)=C([H])C=1[H])(N1C([H])([H])C([H])([H])C2=C([H])C3=C(C([H])=NN3C3C([H])=C([H])C(=C([H])C=3[H])F)C([H])([H])[C@]2(C(C2=C([H])C([H])=C([H])C([H])=N2)=O)C1([H])[H])(=O)=O
|
| InChi Key |
VXOBXKQLNWYQPQ-NDEPHWFRSA-N
|
| InChi Code |
InChI=1S/C29H22F4N4O3S/c30-22-6-8-23(9-7-22)37-26-15-21-12-14-36(41(39,40)24-10-4-20(5-11-24)29(31,32)33)18-28(21,16-19(26)17-35-37)27(38)25-3-1-2-13-34-25/h1-11,13,15,17H,12,14,16,18H2/t28-/m0/s1
|
| Chemical Name |
[(4aR)-1-(4-fluorophenyl)-6-[4-(trifluoromethyl)phenyl]sulfonyl-4,5,7,8-tetrahydropyrazolo[3,4-g]isoquinolin-4a-yl]-pyridin-2-ylmethanone
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7165 mL | 8.5827 mL | 17.1653 mL | |
| 5 mM | 0.3433 mL | 1.7165 mL | 3.4331 mL | |
| 10 mM | 0.1717 mL | 0.8583 mL | 1.7165 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Link: https://clinicaltrials.gov/ct2/show/NCT05407324
Conditions:Amyotrophic Lateral SclerosisLink: https://clinicaltrials.gov/ct2/show/NCT06495944
Conditions:Healthy AdultsLink: https://clinicaltrials.gov/ct2/show/NCT06928779
Conditions:Hepatic Impairment
Title:Safety, Tolerability, and Pharmacokinetic Study of CORT113176 in Healthy Participants
Status:Completed
updateDate:2021-10-11
Ctid:NCT04994743
Link: https://clinicaltrials.gov/ct2/show/NCT04994743
Conditions:Healthy AdultsProducts are for research use only; We do not sell to patients
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